A controversial late goal from Nani and a first-half header by Manchester United captain Nemanja Vidic ensured a 2-1 win which meant Tottenham's 21-year wait for victory at Old Trafford continued.
United captain Vidic opened the scoring after 31 pulsating minutes before Nani reacted quickest to some goalmouth confusion to prod home five minutes from time.
Spurs, who have not won at the ground since 1989, were furious with referee Mark Clattenburg for allowing the second, scored after goalkeeper Heurelho Gomes placed what he believed to be a dead ball.
With just two minutes gone, Park Ji-sung went close to giving United the lead. His low effort had Gomes well beaten but cannoned off the post to safety.
Rafael van der Vaart then matched Park's earlier effort, holding possession despite tumbling to the floor before rising to curl the ball against the far post.
A clumsy Younes Kaboul challenge after half an hour gave the Red Devils the chance to attack from a set-piece and they duly cashed in. Nani floated in the free-kick in from the left and Vidic eased in front of Benoit Assou-Ekotto to head home.
Dimitar Berbatov could have doubled the lead over his old club just before the interval, only for a combination of Gomes and William Gallas to stifle him.
In the 59th minute, Gareth Bale finally gave the away support something to cheer as he bore down on goal, only to see his shot squirm just wide of Van der Sar's far post.
Nani's controversial strike ended matters, with Clattenburg judging play to be still active when Gomes placed the ball down in his area after an unsuccessful penalty appeal.
Gomes clearly believed he was lining up a dead ball but the Portuguese winger was the only one on the referee's wavelength and rolled the ball in to tee up furious scenes of protest by the visitors.